Dynamic measurement of altered chemical messenger secretion after cellular uptake of nanoparticles using carbon-fiber microelectrode amperometry

In this work, carbon-fiber microelectrode amperometry is used to characterize serotonin exocytosis from murine peritoneal mast cells cocultured with fibroblasts in the presence of Au nanoparticles. In the case of mast cell exposure to 1 nM 28 nm diameter spherical Au nanoparticles, there is a decrease of greater than 30% in the number of successful granule transport and fusion events, greater than 30% increase in the rate of intragranular matrix expansion, and greater than 20% increase in the number of secreted serotonin molecules per granule. These results suggest that nanoparticles interrupt the dense-core biopolymer intragranular matrix and present the potential for systematic studies showing how exocytotic function is influenced by nanoparticle size, shape, and composition.     

Trade-Off Between Sensitivity and Specificity in the Cabbage Looper Moth Response to Sex Pheromone

The evolution of male moth responses to pheromone blends may be constrained by a trade-off between two response traits: sensitivity and breadth of response. Population genetic simulations predict that if sensitivity and breadth of response are negatively correlated (i.e., a trade-off exists), then selection will favor males with narrow response phenotypes and high sensitivity. Although sensitivity-breadth of response trade-offs are generally assumed to exist and are implicit to the shape of male preference function, this study is the first to provide empirical support measuring behavior at the level of the individual. Previous studies with the cabbage looper, Trichoplusia ni, have documented the existence of a mutant pheromone strain. While mutant females produce a pheromone blend significantly different from wild-type females, mutant males respond equally to the wild-type and mutant pheromone blends. This study used wind tunnel bioassays to document that relative to wild-type males, mutant males had broader response profiles but lower pheromone sensitivity. While wild-type male responses were highest to the wild-type pheromone blend, mutant males did not discriminate among pheromone blends. These results are consistent with a trade-off between breadth of response and sensitivity. Pure wild-type and mutant lines were crossed and hybrid males assayed. Both hybrid types (maternal wild-type and maternal mutant hybrids) responded similarly. Hybrid males had response profiles similar to wild-type males and the reduced sensitivity observed in mutant males. These results suggest a possible hybrid disadvantage and a putative mechanism for reinforcement of male pheromone response traits.     

A preclinical system prototype for focused microwave thermal therapy of the breast

A preclinical prototype of a transcutaneous thermal therapy system has been developed for the targeted treatment of breast cancer cells using focused microwaves as an adjuvant to radiation, chemotherapy, and high-intensity-focused ultrasound. The prototype system employs a 2-D array of tapered microstrip patch antennas operating at 915?MHz to focus continuous-wave microwave energy transcutaneously into the pendent breast suspended in a coupling medium. Prior imaging studies are used to ascertain the material properties of the breast tissue, and these data are incorporated into a multiphysics model. Time-reversal techniques are employed to find a solution (relative amplitudes and phase) for focusing at a given location. Modeling tests of this time-reversal focusing method have been performed, which demonstrate good targeting accuracy within heterogeneous breast tissue. Experimental results using the laboratory prototype to perform focused heating in tissue-mimicking gelatin phantoms have demonstrated 1.5-cm-diameter focal spot sizes and differential heating at the desired focus sufficient to achieve an antitumor effect confined to the target region.     

Achromatic half-wave plate for submillimeter instruments in cosmic microwave background astronomy: experimental characterization

An achromatic half-wave plate (HWP) to be used in millimeter cosmic microwave background (CMB) polarization experiments has been designed, manufactured, and tested. The design is based on the 5-plates Pancharatnam recipe and it works in the frequency range 85-185 GHz. A model has been used to predict the transmission, reflection, absorption, and phase shift as a function of frequency. The HWP has been tested by using coherent radiation from a back-wave oscillator to investigate its modulation efficiency and with incoherent radiation from a polarizing Fourier transform spectrometer (FTS) to explore its frequency behavior. The FTS measurements have been fitted with an optical performance model which is in excellent agreement with the data. A detailed analysis of the data also allows a precise determination of the HWP fast and slow axes in the frequency band of operation. A list of the HWP performance characteristics is reported including estimates of its cross polarization.     

Preparation of N-sulfonyl- and N-carbonyl-11-azaartemisinins with greatly enhanced thermal stabilities: in vitro antimalarial activities

As the clinically used artemisinins do not withstand the thermal stress testing required to evaluate shelf life for storage in tropical countries where malaria is prevalent, there is a need to develop thermally more robust artemisinin derivatives. Herein we describe the attachment of electron-withdrawing arene- and alkanesulfonyl and -carbonyl groups to the nitrogen atom of the readily accessible Ziffer 11-azaartemisinin to provide the corresponding N-sulfonyl- and -carbonylazaartemisinins. Two acylurea analogues were also prepared by treatment of the 11-azaartemisinin with arylisocyanates. Several of the N-sulfonylazaartemisinins have melting points above 200 degrees C and possess substantially greater thermal stabilities than the artemisinins in current clinical use, with the antimalarial activities of several of the arylsulfonyl derivatives being similar to that of artesunate against the drug-sensitive 3D7 clone of the NF54 isolate and the multidrug-resistant K1 strain of P. falciparum. The compounds possess relatively low cytotoxicities. The carbonyl derivatives are less crystalline than the N-sulfonyl derivatives, but are generally more active as antimalarials. The N-nitroarylcarbonyl and arylurea derivatives possess sub-ng ml(-1) activities. Although several of the azaartemisinins possess log P values below 3.5, the compounds have poor aqueous solubility (<1 mg L(-1) at pH 7). The greatly enhanced thermal stability of our artemisinins suggests that strategic incorporation of electron-withdrawing polar groups into both new artemisinin derivatives and totally synthetic trioxanes or trioxolanes may assist in the generation of practical new antimalarial drugs which will be stable to storage conditions in the field, while retaining favorable physicochemical properties.     

On the CFD modelling of Taylor flow in microchannels

With the increasing interest in multiphase flow in microchannels and advancement in interface capturing techniques, there have recently been a number of attempts to apply computational fluid dynamics (CFD) to model Taylor flow in microchannels. The liquid film around the Taylor bubble is very thin at low Capillary number (Ca) and requires careful modelling to capture it. In this work, a methodology has been developed to model Taylor flow in microchannel using the ANSYS Fluent software package and a criterion for having a sufficiently fine mesh to capture the film is suggested. The results are shown to be in good agreement with existing correlations and previous valid modelling studies. The role played by the wall contact angle in Taylor bubble simulations is clarified.     

The effects of the myostatin g+6723G>A mutation on carcass and meat quality of lamb

This study evaluated the effects of the myostatin g + 6723G > A mutation on carcass and meat quality traits of lamb (AA: n = 5; AG: n = 8; GG: n = 9). Dressing percentage was positively affected by the mutation with homozygotes for the mutation having the highest yield. Regarding carcass composition, there was a significant increase in the proportional weights of the loin and hindquarter muscles. Objective meat quality traits of the M. longissimus lumborum (LL) and M. semimembranosus (SM) were not significantly affected. For the SM, toughness (shear force and compression) tended to be lowest for homozygotes for the mutation. The myostatin g + 6723G > A mutation did not affect sensory meat quality traits of grilled steaks for the LL, but resulted in a significant improvement in eating quality for the SM. Given the number of animals in this study, the robustness of the outcome of this study with regard to the effects on meat quality and its causes requires further investigation.     

Candida glabrata Ste20 is involved in maintaining cell wall integrity and adaptation to hypertonic stress, and is required for wild-type levels of virulence

The conserved family of fungal Ste20 p21-activated serine-threonine protein kinases regulate several signalling cascades. In Saccharomyces cerevisiae Ste20 is involved in pheromone signalling, invasive growth, the hypertonic stress response, cell wall integrity and binds Cdc42, a Rho-like small GTP-binding protein required for polarized morphogenesis. We have cloned the STE20 homologue from the fungal pathogen Candida glabrata and have shown that it is present in a single copy in the genome. Translation of the nucleotide sequence predicts that C. glabrata Ste20 contains a highly conserved p21-activated serine-threonine protein kinase domain, a binding site for G-protein beta subunits and a regulatory Rho-binding domain that enables the kinase to interact with Cdc42 and/or Rho-like small GTPases. C. glabrata Ste20 has 53% identity and 58% predicted amino acid similarity to S. cerevisiae Ste20 and can complement both the nitrogen starvation-induced filamentation and mating defects of S. cerevisiae ste20 mutants. Analysis of ste20 null and disrupted strains suggest that in C. glabrata Ste20 is required for a fully functional hypertonic stress response and intact cell wall integrity pathway. C. glabrata Ste20 is not required for nitrogen starvation-induced filamentation. Survival analysis revealed that C. glabrata ste20 mutants, while still able to cause disease, are mildly attenuated for virulence compared to reconstituted STE20 cells.     

Comparison of ward population estimates from FHSA patient registers with the 1991 Census

"Postcode addresses from National Health Service patient registers for Norfolk and Suffolk [counties in England] current on census day 1991 were assigned to census wards, and estimates of populations in wards were produced for the total population and for twelve age-sex groups. These were compared with adjusted counts of usual residents from the 1991 Census." The results indicate that family health service authority registers "are an acceptable alternative to the census for population estimation purposes. This supports recent arguments for wider use of population registers and suggests that they may be particularly valuable as a source of intercensal information."